Increased in vitro tetanus-induced production of HIV type 1 following in vivo immunization of HIV type 1-infected individuals with tetanus toxoid

We have previously demonstrated that immunization of HIV-l-infected individuals with the common recall antigen, tetanus, induced transient increases in plasma viremia as well as an increased ability to isolate virus from CD8(+) T cell-depleted peripheral blood mononuclear cells (PBMCs) under minimally stimulated culture conditions (IL-2 plus IL-4) postimmunization, In this study, HIV-l-infected individuals were immunized with tetanus toroid and PBMCs were examined at multiple time points following immunization, Tetanus-induced production of virus was defined as an increased ability to isolate HIV-1 from CD8(+) T cell-depleted PBMCs in vitro in the presence of tetanus antigen as opposed to no antigen or control antigen alone, Following immunization, in vitro tetanus-induced production of HIV-1 was observed in 8 of 13 (62%) patients compared to 2 of 13 (15%) patients prior to immunization. In four of these patients, virus could also be isolated from CD8(+) T cell-depleted PBMCs in the presence of tetanus without the addition of any exogenous IL-2, Furthermore, virus could be isolated from the unfractionated PBMCs of two patients when tetanus antigen alone was added to the culture in the absence of added PHA or PHA blasts, HIV-1 was isolated predominantly from CD4(+) T cells with a CD45RO(+), CD25(+) phenotype and was associated with a trend to elevated levels in culture supernatants of IFN-gamma, IL-6, TNF-alpha, and IL-4. These findings have important implications with regard to the role of ongoing antigen-specific immune responses in the induction of HIV-1 expression in vivo.